Deep brain stimulation (DBS) is an effective neurosurgical approach for a variety of neurological and psychiatric disorders including Parkinson's disease, essential tremor, epilepsy, and depression, among others. This research proposal is intended to advance DBS technology by developing a novel intraoperative monitoring approach based on electrochemical monitoring at the brain-electrode interface by use of carbon nanofiber (CNF) based electrode design. This approach utilizes technology developed at the Mayo Clinic, the Wireless Instantaneous Neurotransmitter Concentration Sensor (WINCS), an instrumentation system that combines digital telemetry with fast-scan cyclic voltammetry (FSCV) and amperometry, coupled to CNF based electrode technology developed at National Aeronautic and Space Administration (NASA) called WINCSnanotrode. Under Mayo IRB approved protocol, WINCS safety and feasibility has already been tested successfully in human patients undergoing DBS neurosurgery. Recently, CNF nanoelectrodes have been shown to be an excellent substrate for electrochemical detection demonstrating ultra high sensitivity, high signal to noise ratio, and rapid sampling, while at the same time providing an improved brain-electrode interface for more efficient stimulation, thereby conserving battery life. By virtue of its sub-second, chemically resolved recording, FSCV is recognized as state-of-the-art for measuring neurotransmitters, including dopamine, serotonin, norepinephrine, and adenosine, in laboratory animals. By correlating the release of neurotransmitter and therapeutic stimulation in real time, Mayo Clinic's WINCS coupled to NASA's WINCSnanotrode will provide a powerful new tool to assess the mechanism of DBS, guiding electrode placement, and testing accuracy and efficiency of stimulation. The three Specific Aims are (1) complete WINCS and WINCSnanotrode development to generate a device that is capable of use in humans for electrochemical sensing, (2) establish WINCSnanotrode approach for intraoperative neurochemical monitoring in a large-animal (pig) model of DBS neurosurgery, and (3) establish WINCS and WINCSnanotrode approach for intraoperative neurochemical monitoring in humans during DBS neurosurgery. We believe that WINCS and WINCSnanotrode technology engenders great potential to identify specific targets for DBS, to streamline the already long and difficult implantation procedure, to assess efficiency of stimulation parameter, and to improve the accuracy and efficiency of stimulating electrode. PUBLIC HEALTH RELEVANCE: Deep brain stimulation (DBS) is an effective neurosurgical treatment for Parkinson's disease and other debilitating neuropathologies. The goal of this proposal is to develop a robust carbon nanofiber based electrochemical electrode capable of use in human DBS patients.